questions 4

Humoral-Mediated Immunity

Topic updated on 03/19/17 2:24am

Biological role
  • Primary function is production of antibodies
    • defense against extracellular threats
      • e.g. bacteria, toxins
  • Main effector cell is B-cell
    • matures into antibody secreting plasma cell
Activation of Humoral-Mediated Immunity

  • Stimulated by two types of antigens 
    • thymus-dependent
      • direct contact of B cell with Th cell needed
        • T-Cell Receptor (TCR) binds with MHC II on the B-cell
          • MHC can only recognize peptides
          • stabilized by CD4
        • CD28 (T-cell) binds with B7 (B-cell)
        • joined cells = conjugate
      • T-cell now a Th2 cell
      • B-cell upregulates CD40 and joins with CD40L on the T-cell
      • cytokines released by Th2
        • IL-4, 5, 6, 13, TGF-β
          • signal for B-cell
            • activation
            • class switch from IgM
            • memory
      • lack of CD40L = Hyper-IgM syndrome
      • reason bacterial capsular vaccines bound to a peptide component
        • ex. H. influenzae
    • thymus-independent
      • non-peptide antigens
        • includes LPS or capsular polysaccharides
      • function in two ways
        • direct activation of B-cells
          • proliferation and secretion of antibodies
        • mitogen
          • stimulate B-cell division in all B-cells
            • no antigenic specificity
      • response
        • weaker than thymus-dependent
        • no memory
        • no class switching
          • only IgM secreted
Primary response
  • Mediated mainly through IgM
    • strengths
      • effective at "trapping" free antigen
      • best at complement activation
    • weakness
      • cannot assist in opsonization
      • cannot mediate antibody-dependent cell-mediated cytoxcitiy (ADCC)
        • see topic
  • Can be produced by thymus-independent antigen
  • Clinical relevance
    • can measure stage of infection
      • early
        • IgM >> IgG
      • late
        • IgG >> IgM
Isotype switching
  • Process of removing constant regions μ (IgM) and δ (IgD) via DNA rearrangement
    • irreversible
    • occurs in germinal centers
  • B-cell/plasma cell can now produce IgG, IgE, IgA but no longer IgM, IgD
    • ↑ afinity
    • ↓ avidity
    • control of which antibody ultimately produced is determined by specific cytokines
      • IL-4 produces IgE  
      • IL-5 produces IgA
  • Occurs when antigen is encountered
  • Mediated by rag
  • Deficiency in isotype switching
    • selective Ig deficiency
    • transient hypogammaglobulinemia of infancy
Secondary response
  • Mediated mainly through IgG
    • strengths
      • only Ig that assists in opsonization
      • complement activation
      • only Ig that can mediate ADCC
  • Different antibodies have different specific functions and properties
    • IgA
      • inhibits binding of pathogens to mucosal surfaces
      • does not activate complement
    • IgE
      • triggers mast cell release
      • defense against helminth parasites
      • main antibody responsible for type I hypersensitivity reactions
Deficiencies in B-cell maturation
  • Bruton's agammaglobulinemia 
  • Common variable immunodeficiency 


Qbank (4 Questions)

(M1.IM.36) Immunology researchers attempt to characterize the role of several cytokines in a 5-year-old male’s allergic reaction to peanuts. Months after initial exposure to peanuts, the child was brought to the ER with symptoms of anaphylaxis that resolved following epinephrine injection and supportive therapy. Which of the following best describes the role of IL-4 in the child’s response: Topic Review Topic

1. B cell class switching
2. Stimulates IgA production
3. Macrophage and Th1 cell activation
4. Neutrophil chemotaxis
5. Growth of cytotoxic T cells

(M1.IM.56) A 12-year-old African American is exposed to pollen while playing outside. The allergen stimulates TH2 cells of his immune system to secrete a factor that leads to B-cell class switching to IgE. What factor is secreted by the TH2 cell? Topic Review Topic

1. IFN-gamma
2. IL-4
3. IL-17
4. TGF-beta
5. IL-22

(M1.IM.66) Which of the following events is likely to occur in the germinal center? Topic Review Topic

1. Development of early pro-B cells
2. Development of immature B cells
3. T-cell negative selection
4. Isotype switching
5. Formation of double-positive T cells

(M1.IM.73) The only immunoglobulin found as a dimer has what primary function? Topic Review Topic

1. Protect against invasive helminth infection
2. Protect against viral infections
3. Provide an initial humoral immune response to newly presenting bacterial antigens
4. Inhibiting bacterial adherance and colonization of mucous membranes
5. Provides the most specific recognition to circulating antigens in the bloodstream


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